A Study to Evaluate the Efficacy, Pharmacodynamics, Safety, and Immunogenicity of FKS518 in Postmenopausal Women With Osteoporosis

NCT ID: NCT04934072

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 553 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-16
• Study Completion Date: 2023-08-07

Brief Summary

The primary objective of this study is to demonstrate equivalent efficacy of the proposed biosimilar denosumab FKS518 to US-licensed Prolia in women with postmenopausal osteoporosis (PMO).

Conditions

Postmenopausal Osteoporosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

FKS518

FKS518 was administered on Day 1, and then every 26 weeks (6 months), i.e., Week 26 and Week 52, at a dose of 60 mg for a total of 3 administrations.

Group Type: EXPERIMENTAL

FKS518

Intervention Type: DRUG

subcutaneously by single-use prefilled syringe (PFS)

US-Prolia

US-Prolia was administered on Day 1, and then every 26 weeks (6 months), i.e., Week 26 and Week 52, at a dose of 60 mg for a total of 3 administrations.

Group Type: ACTIVE_COMPARATOR

US-licensed Prolia (Amgen)

Intervention Type: DRUG

subcutaneously by single-use PFS

Interventions

FKS518

subcutaneously by single-use prefilled syringe (PFS)

Intervention Type: DRUG

US-licensed Prolia (Amgen)

subcutaneously by single-use PFS

Intervention Type: DRUG

Other Intervention Names

Denosumab biosimilar; Denosumab

Eligibility Criteria

Inclusion Criteria

1. Female ≥55 to ≤85 years of age, inclusive, at screening.

2. Have a body mass index (BMI) ≥18 to ≤32 kg/m^2.

3. Participant should have confirmed postmenopausal status, defined as age-related or early/premature amenorrhea ≥12 consecutive months and increased follicle-stimulating hormone (FSH) >40 mIU/mL at screening; or surgical menopause (bilateral oophorectomy with or without hysterectomy) ≥12 months prior to screening.

4. Absolute bone mineral density (BMD) consistent with T-score ≤-2.5 and ≥-4.0 at the lumbar spine as measured by dual energy x-ray absorptiometry (DXA) as per central assessment.

5. At least 2 vertebrae in the lumbar vertebrae 1 to lumbar vertebrae 4 (L1-L4) region and at least 1 hip joint are evaluable by DXA.

6. Clinically acceptable physical examinations and laboratory tests and no history or evidence of any clinically significant concomitant medical disorder that, in the opinion of the Investigator, would pose a risk to participant safety or interfere with study evaluations or procedures.

7. Written informed consent including accepting a separate Information Sheet containing important information about COVID-19 and its general risks for participants participating in the clinical trial.

Exclusion Criteria

Disease-related

1. History and/or presence of 1 severe or >2 moderate vertebral fractures or hip fracture confirmed by x-ray.

2. Presence of active healing fracture at screening.

3. History and/or presence of bone-related disorders, such as but not limited to Paget's disease, osteomalacia, hyperparathyroidism (or parathyroid disorders), or renal osteodystrophy.

4. Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (eg, tooth extraction, dental implants, or oral surgery in the past 6 months), poor oral hygiene, periodontal, and/or pre-existing dental disease as assessed by the Investigator.

5. Evidence of hypocalcemia (albumin-adjusted serum calcium <2.13 mmol/L or <8.5 mg/dL) or hypercalcemia (albumin-adjusted serum calcium >2.6 mmol/L or >10.5 mg/dL) as assessed by the central laboratory at screening.

6. Vitamin D deficiency (25-hydroxy vitamin D levels <12 ng/mL) as assessed by central laboratory at screening (retest is allowed once).

7. Known intolerance to calcium or vitamin D supplements.

Other Medical Conditions

8. Known or suspected clinically relevant drug hypersensitivity to any components of the study drug, comparable drugs, or to latex.

9. Renal impairment: creatinine clearance <30 mL/min at screening or receiving dialysis.

10. Medical evidence of current or history of primary or secondary immunodeficiency.

11. Infection-related exclusions as further defined in the protocol.

12. Major surgical procedure within 8 weeks prior to the screening or scheduled during the study.

13. Current or history of any malignancy, or myeloproliferative, or lymphoproliferative disease within 5 years before screening.

14. History of clinically significant drug or alcohol abuse within the last year prior to randomization.

15. Prior denosumab (Prolia, Xgeva, or proposed denosumab biosimilar) exposure.

16. Prior use of fluoride within the 5 years before inclusion in the study.

17. Any current or prior use of strontium ranelate.

18. Any current or prior use of intravenous bisphosphonates.

19. Current or prior use of teriparatide and other parathormone (PTH) analogues within 12 months before screening.

20. Current or prior use of systemic oral or transdermal estrogen or selective estrogen receptor modulators or tibolone within 6 months before screening.

21. Current or prior use of calcitonin or cinacalcet within 3 months before screening or any cathepsin K inhibitor (eg, odanacatib) within 18 months before screening.

22. Current or prior use of romosozumab or antisclerostin antibody.

23. Current or prior use of other osteoporotic agents used for the prevention or treatment of osteoporosis.

24. Current use within 3 months before screening of any medication with known influence on the skeletal system (eg, systemic corticosteroids, heparin, lithium, etc) with exceptions described in the protocol.

25. Concomitant treatment with another biologic drug.

26. Have received a COVID-19 vaccine within 4 weeks before randomization or COVID-19 vaccination is ongoing at the time of screening.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fresenius Kabi SwissBioSim GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Diagnostic Consultative Center Aleksandrovska

Sofia, Sofia-Grad, Bulgaria

Diagnostic Consultative Center (DCC) 17 - Sofia

Sofia, Sofia-Grad, Bulgaria

Medical Center N. I. Pirogov

Sofia, Sofia-Grad, Bulgaria

Medical Center Hipokrat 2000 OOD

Haskovo, , Bulgaria

Medical Center Medconsult Pleven

Pleven, , Bulgaria

Palmed University Multidisciplinary Hospital for Active Treatment

Plovdiv, , Bulgaria

University Multi-profile Hospital for Active Treatment - Plovdiv

Plovdiv, , Bulgaria

Medical Center - Teodora EOOD

Rousse, , Bulgaria

Multiprofile Hospital for Active Treatment Hadzhi Dimitar

Sliven, , Bulgaria

Lyulin Hospital

Sofia, , Bulgaria

Diagnostic and Consultative Center Equita

Varna, , Bulgaria

Medical Center Sanador M

Vidin, , Bulgaria

CCR Brno

Brno, Jihormoravsky Kraj, Czechia

CCR Ostrava

Ostrava, Severomoravsky Kraj, Czechia

Medical Plus

Uherské Hradiště, South Moravian, Czechia

G-Centrum Olomouc s.r.o

Olomouc, , Czechia

Artroscan

Ostrava-T?ebovice, , Czechia

Medical Plus

Uherské Hradiště, , Czechia

Center for Clinical and Basic Research AS - Tallinn

Tallinn, Harju, Estonia

Sihtasutus Pohja-Eesti Regionaalhaigla

Tallinn, Harju, Estonia

KLV Arstikabinet

Pärnu, Pärnumaa, Estonia

Tartu Ulikooli Kliinikum

Tartu, Tartu, Estonia

KLV Arstikabinet

Pärnu, , Estonia

Evex Hospitals - Caraps Medline

Tbilisi, Borjomi, Georgia

Georgian-Dutch Hospital

Tbilisi, Borjomi, Georgia

Hepatology Clinic Hepa

Tbilisi, , Georgia

Tbilisi Heart And Vascular Clinic Ltd

Tbilisi, , Georgia

Jerarsi Clinic

Tbilisi, , Georgia

Raymann - Clinic of Raymann Doctors

Tbilisi, , Georgia

MedCity Ltd.

Tbilisi, , Georgia

Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar

Szeged, Csongr, Hungary

Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar

Szeged, Csongrád megye, Hungary

Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz

Szentes, Csongrád megye, Hungary

Szent Anna Magan N?gyogyaszati

Debrecen, Hajdú-Bihar, Hungary

Markhot Ferenc Oktatokorhaz es Rendel?intezet

Eger, Heves County, Hungary

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, Pest County, Hungary

Obudai Egeszsegugyi Centrum

Zalaegerszeg, Zala County, Hungary

Drug Research Center Balatonfured

Balatonfüred, , Hungary

Revita Rendel?

Budapest, , Hungary

Clinexpert Gyogycentrum

Budapest, , Hungary

Obudai Egeszsegugyi Centrum

Budapest, , Hungary

Semmelweis Egyetem - I. sz. Belgyogyaszati Klinika

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont Kenezy Gyula Campus

Debrecen, , Hungary

Markhot Ferenc Oktatokorhaz es Rendel?intezet

Eger, , Hungary

Kalocsai Szent Kereszt Korhaz

Kalocsa, , Hungary

CMed Rehabilitacios es Diagnosztikai Kozpont / Saldinvest Kft.

Székesfehérvár, , Hungary

Vital Medical Center - Reumatologia

Veszprém, , Hungary

Centrum Medyczne Solumed

Pozna?, Greater Poland Voivodeship, Poland

Centrum Bada? Klinicznych

Poznan, Greater Poland Voivodeship, Poland

Nasz Lekarz Przychodnie Medyczne

Torun, Kuyavian-Pomeranian Voivodeship, Poland

Centrum Medyczne All-Med

Krakow, Lesser Poland Voivodeship, Poland

Pratia MCM Krakow

Krakow, Lesser Poland Voivodeship, Poland

FutureMeds

Wroclaw, Lower Silesian Voivodeship, Poland

Wromedica Centrum Zdrowia

Wroclaw, Lower Silesian Voivodeship, Poland

Centrum Medyczne Oporow

Wroclaw, Lower Silesian Voivodeship, Poland

RCMed Oddzial Sochaczew

Sochaczew, Masovian Voivodeship, Poland

Medycyna Kliniczna

Warsaw, Masovian Voivodeship, Poland

Centrum Medyczne AMED - Warszawa Targowek

Warsaw, Masovian Voivodeship, Poland

Rheuma Medicus - Specjalistyczne Centrum Reumatologii i Osteoporozy

Warsaw, Masovian Voivodeship, Poland

Twoja Przychodnia Szczeci?skie Centrum Medyczne

Warsaw, Masovian Voivodeship, Poland

SOMED CR - ?od?

Warsaw, Masovian Voivodeship, Poland

Osteo-Medic sc dr diabetolog Katarzyna Wasilewska

Bialystok, Podlaskie Voivodeship, Poland

ClinicMed

Bialystok, Podlaskie Voivodeship, Poland

Nasz Lekarz O?rodek Bada? Klinicznych - Bydgoszcz

Bydgoszcz, Pomeranian Voivodeship, Poland

Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy

Bydgoszcz, Pomeranian Voivodeship, Poland

Centrum Medyczne Pratia - Gdynia

Gdynia, Pomeranian Voivodeship, Poland

Centrum Medyczne Pratia - Gdynia

Gdynia, Pomeranian Voivodeship, Poland

Gabinet diagnostyki i leczenia osteoporozy

Gliwice, Silesian Voivodeship, Poland

Centrum Kliniczno Badawcze J Brzezicki B Górnikiewicz Brzezicka Lekarze

Elblag, Warmian-Masurian Voivodeship, Poland

Ambulatorium Sp z o.o. - Elblag

Elblag, Zulawy, Poland

Centrum Medyczne All-Med

Krakow, , Poland

SOMED CR - ?od?

Lodz, , Poland

Twoja Przychodnia - Centrum Medyczne Nowa Sol

Nowa Sól, , Poland

Twoja Przychodnia Szczeci?skie Centrum Medyczne

Szczecin, , Poland

Samodzielny Publiczny Zespo? Opieki Zdrowotnej w Tomaszow Lubelski

Tomaszów Lubelski, , Poland

Klinika Reuma Park sp. z o.o. sp.k - Centrum Medyczne Reuma Park

Warsaw, , Poland

Countries

Bulgaria; Czechia; Estonia; Georgia; Hungary; Poland

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2020-004422-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FKS518-002

Identifier Type: -

Identifier Source: org_study_id